Surface Engineered Dendrimers in siRNA Delivery and Gene Silencing

Author(s):

Abstract:

Background: Therapeutic efficacy of dreadful diseases like cancer, HIV (Human Immunodeficiency Virus) can be enhanced by delivering molecules which regulate function at gene level rather than at receptor level. Silencing RNA is one such approach recently used to silence target gene expressed diseases; and thereby reduce target protein levels. Many of the non-viral vectors are proved to act as carriers for silencing RNA. Dendrimers being one of them have less size, low poly dispersibility index, water solubility, multivalence, and easy surface modification. Many such surface modifications have been carried out to improve the delivery potential of small interfering RNA (siRNA) modified dendrimers compared to simple plain dendrimers.

Methods: Dendrimer was taken as a core whose surface was modified with fluorine, amino acids, phosphate, lipids, folate, specific antibody or RGD (Arg-Gly-Asp). The purpose of these modifications was to increase the therapeutic siRNA efficiency, lower the toxicity and improve the targeting potential of dendrimers.

Conclusion: Thus, surface modified dendrimers render a complete pack which offers increased siRNA loading, increased transfection and permeability, efficient targeting, endosomal escape and protecting siRNA from degradation by RNase and other such enzymes. The objective of this manuscript is to provide different approaches currently available for surface modifications of dendrimers and their overall effect on transfection ability of siRNA to target tissues.

Keywords:

Affiliation:

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Opposite Air Force Station Palaj, Gandhinagar, Gujarat 382355, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Opposite Air Force Station Palaj, Gandhinagar, Gujarat 382355, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Opposite Air Force Station Palaj, Gandhinagar, Gujarat 382355, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Opposite Air Force Station Palaj, Gandhinagar, Gujarat 382355, Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Opposite Air Force Station Palaj, Gandhinagar, Gujarat 382355, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Palaj, Opposite Air Force Station, Gandhinagar, Gujarat 382355